MRI visible bioscaffold for stem cell-mediated repair and improved cardiac function

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC162

Poster Communications: MRI visible bioscaffold for stem cell-mediated repair and improved cardiac function

L. Jackson1, J. Habib2, D. Stuckey1, M. Lythgoe1

1. Centre for Advanced Biomedicla Imaging, University College London, London, United Kingdom. 2. Imaging Sciences and Biomedical Engineering, Kings College London, London, United Kingdom.

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Motivation: The severely limited ability of the heart to repair itself following injury has led to the development of novel cell therapies aimed at stimulating myocardial regeneration (Coulombe et al. 2014). Transplanted bone marrow mononuclear cells (BMCs) are proposed as such a solution owing to their ability to promote myocardial survival by angiogenesis reducing infarct size (Kamihata et al. 2001). This study aimed to use magnetic resonance imaging (MRI) to assess functional change and distribution of intra-myocardial injections of therapeutic BMCs in a MR-visible hydrogel. Methods: Marrow was extracted from adult Wistar rat hind-limbs (n=4) immediately following sacrifice by cervical dislocation, BMCs were isolated by centrifugation then suspended at 107 cells/ml in 2×50µl gadolinium (Gd) doped alginate for injection. Myocardial infarction was induced by ligation of the left anterior descending artery, for surgery and imaging rats were anaesthetised by inhalation of isoflurane and oxygen (2% / 2%). BMCs were either directly injected into the ischemic region during surgery (n=3) or injected closed chest using ultrasound guidance at 7d after infarction (n=3) (fig.1). MRI was performed 3d after injection. A cine-stack covering the left ventricle (LV) (0.4×0.4×1.5mm;TE/TR 1.2/5ms) was acquired to measure LV properties. A pre-Gd inversion recovery (IR) sequence located Gd-doped hydrogel (0.27×0.27×1.5mm; TE/TR 1.6/3.9). After intraperitoneal injection of 0.5mmol/kg Gd-DTPA a 2nd post-Gd IR sequence was acquired to measure infarct size. A tag-cine sequence measured regional contraction (0.2×0.2×1.5mm). Results: Gd-doped bioscaffold was visible pre-Gd, demarcating the region of gel administration (fig.2a). Post-Gd enhanced the ischemic myocardium demonstrating good co-localisation of the therapy and the damaged tissue (fig.2b). Combining this with tag-cine MRI permits the presence of grafted cells to be correlated with changes in regional strain, determining the local effect of therapy on myocardial contractility (fig.2c). Although this study is not currently powered to identify changes in function, the data in table 1 suggest improvement in treated hearts. Conclusion: This work establishes a method for assessment of BMCs as a regenerative cardiac therapy using MRI. This imaging strategy has applications in evaluation of other cell transplantation regeneration therapies, where the impact of bioscaffolds on their local myocardial environment is not well known.



Where applicable, experiments conform with Society ethical requirements.

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